Unwanted stimulation detection during cardiac pacing

ABSTRACT

The disclosure relates to systems and methods for cardiac rhythm management. In some cases, a system may include a pulse generator for generating pacing pulses for stimulating a heart of a patient; a memory; and a sensor configured to sense a response to a unwanted stimulation and to produce a corresponding sensor signal. A processing circuit may receive the sensor signal for a time after one or more pacing pulses, and may derive a time-frequency representation of the sensor signal based on the received sensor signal. The processing circuit may use the time-frequency representation of the sensor signal to help identify unwanted stimulation. Once unwanted stimulation is detected, the processing circuit may change the pacing pulses to help reduce or eliminate the unwanted stimulation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §119 to U.S.Provisional Application Ser. No. 61/872,358, filed Aug. 30, 2013, theentirety of which is incorporated herein by reference.

BACKGROUND

Cardiac rhythm management devices are often implantable devices thatprovide electrical stimulation to selected chambers of the heart inorder to treat disorders of cardiac rhythm. A pacemaker, for example, isa cardiac rhythm management device that paces the heart with timedpacing pulses. The most common condition for which pacemakers are usedis in the treatment of bradycardia, where the ventricular rate is tooslow. Atrio-ventricular conduction defects (i.e., AV block) that arepermanent or intermittent and sick sinus syndrome represent the mostcommon causes of bradycardia for which permanent pacing may beindicated. If functioning properly, the pacemaker makes up for theheart's inability to pace itself at an appropriate rhythm in order tomeet metabolic demand by, for example, enforcing a minimum heart rate.

Pacemakers are usually implanted subcutaneously or submuscularly on apatient's chest and have leads threaded intravenously into the heart toconnect the device to electrodes used for sensing and pacing. Leads mayalso be positioned on the epicardium by various means. A programmableelectronic controller causes the pacing pulses to be output in responseto lapsed time intervals and sensed electrical activity (i.e., intrinsicheart beats not as a result of a pacing pulse). Pacemakers senseintrinsic cardiac electrical activity by means of internal electrodesoften disposed near the chamber to be sensed. A depolarization waveassociated with an intrinsic contraction of the atria or ventricles thatis detected by the pacemaker is referred to as an atrial sense orventricular sense, respectively. In order to cause such a contraction inthe absence of an intrinsic beat, a pacing pulse (either an atrial paceor a ventricular pace) with energy above a certain pacing threshold isdelivered to the appropriate chamber via the same or different electrodeused for sensing the chamber.

Electrical stimulation of the heart through the internal electrodes canalso cause unwanted stimulation of skeletal muscle and/or nerves. Theleft phrenic nerve, which provides innervation for the diaphragm, arisesfrom the cervical spine and descends to the diaphragm through themediastinum where the heart is situated. As it passes the heart, theleft phrenic nerve courses along the pericardium, superficial to theleft atrium and left ventricle. Because of its proximity to theelectrodes used for pacing, particularly for left side pacing, the nervecan be stimulated by a pacing pulse. The resulting involuntarycontraction of the diaphragm can be quite annoying or painful to thepatient, often producing a response that is similar to a hiccup.

SUMMARY

Cardiac rhythm management devices and methods are disclosed forminimizing or eliminating unwanted stimulation of skeletal muscle, suchas phrenic nerve stimulation (PS), while treating disorders of cardiacrhythm and similar disorders. In one example, phrenic nerve stimulationis detected during cardiac pacing. If detected, subsequent cardiacpacing pulses are configured to capture the heart and minimizesubsequent phrenic nerve stimulation. In this context, “capture” refersto causing sufficient depolarization of the myocardium that apropagating wave of excitation and contraction result (i.e., aheartbeat). It is contemplated that all types of cardiac rhythmmanagement devices may benefit including, but not limited to,bradycardia pacing, anti-tachycardia pacing, and cardiacresynchronization pacing.

In the various embodiments, the determination of whether the phrenicnerve of the patient has been stimulated is based at least in part upondata in the frequency domain. In certain embodiments, the determinationof whether the phrenic nerve of the patient has been stimulated by apacing pulse is based at least in part upon a comparison of datagathered by a sensor over at least one cycle of cardiac activity to aspecimen of data which had been previously identified as correspondingto phrenic nerve stimulation; to a specimen of data which had beenpreviously identified as not corresponding to phrenic nerve stimulation;or to a combination of both. In such embodiments, the respectivespecimens of data, which had been previously identified as correspondingto phrenic nerve stimulation and/or which had been previously identifiedas not corresponding to phrenic nerve stimulation, may be one or moresingle instances of the behavior or may include functions of severalinstances of the behavior. The respective specimens of data may beobtained from the patient or may represent an aggregation of specimensfrom more than one patient.

In one example, a system for cardiac rhythm management is provided. Thesystem may include a pulse generator for generating pacing pulses forstimulating a heart of a patient, a memory, and a sensor for sensing aresponse to a stimulation of a phrenic nerve of the patient and toproduce a corresponding sensor signal. A processing circuit may be incommunication with the memory and the sensor. The processing circuit maybe configured to: receive the sensor signal for a time after one or morepacing pulses; derive a time-frequency representation of the sensorsignal based on the received sensor signal using wavelets; identify adominant frequency component in the time-frequency representation of thesensor signal; determine if the dominant frequency component fallswithin a predetermined frequency range; identify a time of occurrence ofthe dominant frequency component relative to a pacing pulse; determineif the time of occurrence of the dominant frequency component occurswithin a predetermined time window; determine if the phrenic nerve ofthe patient has been stimulated based, at least in part, on thetime-frequency representation of the sensor signal such that thedominant frequency component falls within the predetermined frequencyrange and the dominant frequency component occurs within thepredetermined time window; store a phrenic nerve stimulation eventidentifier in the memory if the processing circuit determines that thephrenic nerve of the patient has been stimulated; generate pacing pulsesfor stimulating the heart of a patient that are anticipated to bothcapture the heart and to minimize phrenic nerve stimulation by thegenerated pacing pulses; and determine if capture of the heart has beenachieved.

In another example, a system for cardiac rhythm management is provided,which may include a pulse generator for generating pacing pulses forstimulating a heart of a patient, a memory, and a sensor configured tosense a response to a stimulation of a phrenic nerve of the patient andto produce a corresponding sensor signal. A processing circuit may be incommunication with the memory and the sensor. The processing circuit maybe configured to: receive the sensor signal for two or more pacingpulses; perform spectral analysis of the sampled sensor signal,resulting in a spectral analysis output; compare the spectral analysisoutput to a phrenic nerve stimulation template; determine that thephrenic nerve of the patient has been stimulated if the spectralanalysis output is considered to match the phrenic nerve stimulationtemplate; and store a phrenic nerve stimulation event identifier in thememory if the processing circuit determines that the phrenic nerve ofthe patient has been stimulated. In some cases, the processing circuitmay also generate pacing pulses for stimulating the heart of a patientthat are anticipated to both capture the heart and to minimize phrenicnerve stimulation.

In yet another example, a method is disclosed for determining if thephrenic nerve of a patient has been stimulated by one or more pacingpulses. The method may include receiving a sensor signal for a timeafter one or more pacing pulses, wherein the sensor signal is providedby a sensor that can sense a stimulation of the phrenic nerve of thepatient. The method may further include determining a time-frequencyrepresentation of the sensor signal based on the received sensor signal;identifying a dominant frequency component in the time-frequencyrepresentation of sensor signal; determining if the dominant frequencycomponent falls within a predetermined frequency range; identifying atime of occurrence of the dominant frequency component relative to acorresponding pacing pulse; determining if the time of occurrence of thedominant frequency component occurs within a predetermined time window;and determining if the phrenic nerve of the patient has been stimulatedbased, at least in part, on the time-frequency representation of thesensor signal such that the dominant frequency component falls withinthe predetermined frequency range and the dominant frequency componentoccurs within the predetermined time window. These are just someexamples.

The preceding summary is provided to facilitate an understanding of someof the innovative features unique to the present disclosure and is notintended to be a full description. A full appreciation of the disclosurecan be gained by taking the entire specification, claims, drawings, andabstract as a whole.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic block diagram of an illustrative cardiac rhythmmanagement device;

FIG. 2 is a schematic diagram of an illustrative switching circuit;

FIG. 3 is a block diagram of an illustrative signal processing module;

FIG. 4A shows an illustrative time domain signal that is meant to berepresentative of a sensor output signal provided by an accelerometerthat is located in or on a patient, in the absence of phrenic nervestimulation;

FIG. 4B illustrates the result of a wavelet analysis of the time domainsignal of FIG. 4A;

FIG. 4C shows an illustrative time domain signal that is meant to berepresentative of a sensor output signal provided by an accelerometerthat is located in or on a patient, in the presence of phrenic nervestimulation;

FIG. 4D illustrates the result of a wavelet analysis of the time domainsignal of FIG. 4C;

FIG. 5 is a flow diagram shown an illustrative method of determining ifphrenic nerve stimulation is present or absent;

FIG. 6 is a flow diagram shown another illustrative method ofdetermining if phrenic nerve stimulation is present or absent;

FIG. 7 illustrates a combined histogram of observed frequency centroidsfor wavelets in which phrenic nerve stimulation is present and in whichphrenic nerve stimulation is absent;

FIG. 8 illustrates a combined histogram of observed time intervalcentroids for wavelets in which phrenic nerve stimulation is present andin which phrenic nerve stimulation is absent;

FIG. 9 is a flow diagram showing another illustrative method ofdetermining if phrenic nerve stimulation is present or absent in apatient; and

FIG. 10 illustrates exemplary power spectra representative of thepresence or absence of phrenic nerve stimulation.

DESCRIPTION

The following description should be read with reference to the drawingswherein like reference numerals indicate like elements throughout theseveral views. The drawings, which are not necessarily to scale, are notintended to limit the scope of the disclosure. The description anddrawings illustrate several examples.

All numbers are herein assumed to be modified by the term “about.” Therecitation of numerical ranges by endpoints includes all numberssubsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3,3.80, 4, and 5).

As used in this specification and the appended claims, the singularforms “a”, “an”, and “the” include the plural referents unless thecontent clearly dictates otherwise. As used in this specification andthe appended claims, the term “or” is generally employed in its senseincluding “and/or” unless the content clearly dictates otherwise.

It is noted that references in the specification to “an embodiment”,“some embodiments”, “other embodiments”, “an example”, “anotherexample”, etc., indicate that the embodiment or example described mayinclude a particular feature, structure, or characteristic, but everyembodiment or example may not necessarily include the particularfeature, structure, or characteristic. Moreover, such phrases are notnecessarily referring to the same embodiment or example. Further, when aparticular feature, structure, or characteristic is described inconnection with an embodiment or example, it is contemplated that suchfeature, structure, or characteristic can be used in connection withother embodiments and other examples, whether or not explicitlydescribed unless clearly stated to the contrary.

A schematic block diagram of a multi-site pacemaker having an atrial andtwo ventricular pacing channels is shown in FIG. 1. It will beappreciated that the device described in FIG. 1 is described for thepurpose of providing context for the subsequent discussion, and shouldnot be view as limiting the scope of the disclosure to that particulardevice. In FIG. 1, the pacemaker may include a control unit thatincludes a controller 10 communicating with a memory 12 via abidirectional data bus, where the memory 12 typically includes a ROM(read-only memory) for program storage and a RAM (random-access memory)for data storage. The control unit of the pacemaker also could beimplemented by other types of processing circuitry, such as discretecomponents, a programmable logic array, a microcontroller, a statemachine, and/or any other suitable processing circuitry as desired.

In some instances, the control unit of the pacemaker may be capable ofoperating the pacemaker in a number of programmed modes where aprogrammed mode defines how pacing pulses are output in response tosensed events and/or expiration of time intervals. Bradycardia pacingmodes refer to pacing algorithms used to pace the atria and/orventricles when the intrinsic atrial and/or ventricular rate isinadequate due to, for example, AV conduction blocks or sinus nodedysfunction. Such modes may include either single-chamber pacing, whereeither an atrium or a ventricle is paced, or dual-chamber pacing inwhich both an atrium and a ventricle are paced. Another type of pacingis anti-tachycardia pacing where the heart is paced competitively inorder to slow an abnormally fast rhythm. Pacemakers can also be employedto improve the coordination of cardiac contractions by timed pacing ofselected chambers or sites (e.g. left and right ventricles), termedcardiac resynchronization therapy (CRT).

Additional sensing of physiological data may help the pacemaker changethe rate at which it paces the heart in accordance with some parametercorrelated to metabolic demand, often referred to as rate-adaptivepacing. One such parameter is the activity level of the patient. In thedevice of FIG. 1, an exertion level sensor 330, which may include, forexample, one or more of an accelerometer, minute ventilation sensor,electrical signal sensor, pressure sensor, an acoustic sensor, and thelike, may sense changes in the patient's physical activity. These orother sensors, which are provided on or in the patient, may beconfigured to provide a sensor signal that is indicative of a responseto a stimulation of the phrenic nerve of the patient. In some instances,the sensor signal provided by the exertion level sensor 330 or othersensor may be filtered by the sensor 330 or may be filtered oncereceived by the controller 10. A telemetry interface 80 is oftenprovided for facilitating communication with an external programmer.

For the purpose of brevity in providing an illustrative example, thediscussion herein will focus on an accelerometer as a representativesensor. However, it is contemplated that any suitable sensor may beused, including sensors that are suitable for sensing muscle or nervestimulation such as phrenic nerve stimulation. When the sensor is anaccelerometer, it may be a single-axis accelerometer, a two-axisaccelerometer, or a three-axis accelerometer, wherein the accelerometersmay be discrete or may be integrated. Multi-axis accelerometers willtypically be configured such that the axes of the various accelerometersare not aligned and may be configured such that the axes of theaccelerometers are substantially mutually orthogonal. Such multi-axisaccelerometers may be used to further distinguish movements along theheight axis of the recipient, which may correspond to diaphragm motions,from movements at right angles to the height axis, which more typicallymay correspond to heart movements or incidental movements such mayresult from an object bumping the chest. When multi-axis accelerometersignals are present, the individual signals may each be processed asdescribed herein and the results of the analysis combined thereafter orthe signals from the several accelerometers may be combined to derive anacceleration vector the direction of which is factored into the analysisto be described herein. This should not be taken as disparaging othersensor types.

In order for a pacemaker to control the heart rate in the mannerdescribed above, the pacing pulses delivered by the device must achieve“capture,” which refers to causing sufficient depolarization of themyocardium that a propagating wave of excitation and contraction result(i.e., a heartbeat). A pacing pulse that does not capture the heart isthus an ineffective pulse. This not only wastes energy from the limitedenergy resources (battery) of the pacemaker, but can have deleteriousphysiological effects as well, since a pacemaker that is not achievingcapture is not performing its function in enforcing a minimum heartrate. A number of factors can determine whether a given pacing pulsewill achieve capture including, for example, the energy of the pulse,which is a function of the pulse's amplitude and duration or width, andthe integrity and physical disposition of the pacing lead.

A pacing pulse must exceed a minimum energy value, or capture threshold,to produce a corresponding contraction of the heart. It is desirable fora pacing pulse to have sufficient energy to stimulate capture of theheart without expending energy significantly in excess of the capturethreshold. Thus, accurate determination of the capture threshold mayprovide efficient pace energy management. If the pacing pulse energy istoo low, the pacing pulses may not reliably produce a contractileresponse in the heart and may result in ineffective pacing. If thepacing pulse energy is too high, the patient may experience discomfortdue to unwanted extracardiac stimulation and/or the battery life of thedevice will be shortened.

A common technique used to determine if capture is present during agiven cardiac cycle is to look for an “evoked response” immediatelyfollowing a pacing pulse. The evoked response is the wave ofdepolarization that results from the pacing pulse and evidences that thepaced chamber has responded appropriately and contracted. By detectingan evoked P-wave and/or evoked R-wave, the pacemaker may be able todetect whether the pacing pulse (A-pulse and/or V-pulse) was effectivein capturing the heart, that is, in causing a contraction in therespective heart chamber.

In order for a pacemaker to detect whether an evoked P-wave and/or anevoked R-wave occurs immediately following an A-pulse or a V-pulse, aperiod of time, referred to as the atrial capture detection window orthe ventricular capture detection window, respectively, starts after thegeneration of the corresponding pacing pulse. Sensing channels arenormally rendered refractory (i.e., insensitive) for a specified timeperiod immediately following a pacing pulse in order to prevent thepacemaker from mistaking a pacing pulse or after potential for anintrinsic beat. This is done by the pacemaker controller ignoring sensedevents during the refractory intervals, which are often defined for bothatrial and ventricular sensing channels and with respect to both atrialand ventricular pacing events. Furthermore, a separate period thatoverlaps the early part of a refractory interval is also defined, calleda blanking interval during which the sense amplifiers are blocked fromreceiving input in order to prevent their saturation during a pacingpulse. If the same sensing channels are used for both sensing intrinsicactivity and evoked responses, the capture detection window is oftendefined as a period that supersedes the normal refractory period so thatthe sensing circuitry within the pacemaker becomes sensitive to anevoked P-wave and/or R-wave.

Capture verification can be performed by delivering a pacing pulse andattempting to sense an evoked response using either the same ordifferent electrodes used for pacing. In the illustrative device shownin FIG. 1, a capture verification test is performed using a dedicatedevoked response sensing channel that includes a sense amplifier 51 forsensing an evoked response generated after a pacing pulse is delivered.The amplifier input of the evoked response sensing channel is switchedvia a switching circuit 70 to selected electrodes of the sensing/pacingchannels before the capture verification test is performed. Afterswitching the input of the evoked response sensing channel to theselected electrodes, a pacing pulse is output and an evoked response iseither detected within the capture detection window or not, signifyingthe presence or loss of capture, respectively.

Although the same electrodes can be used for pacing and evoked responsedetection during a capture verification test, the input of the evokedresponse sensing channel may be switched to electrodes of anothersensing/pacing channel. The particular electrodes used for evokedresponse detection can be selected in accordance with which electrodesproduce a sensing vector that most easily senses an evoked response dueto the pacing electrodes. The sense amplifier 51 of the evoked responsesensing channel is then blanked during the capture verification test fora specified blanking period following a pacing pulse output by thetested sensing/pacing channel. The blanking period is followed by acapture detection window during which an evoked response may be sensedby the evoked response sensing channel. In some cases, the blankingperiod may be approximately 10 ms, and the width of the capturedetection window may range from 50 to 350 ms, but these are justexamples.

The illustrative pacemaker may have an atrial sensing/pacing channelthat includes ring electrode 43 a, tip electrode 43 b, sense amplifier41, pulse generator 42, and an atrial channel interface 40 whichcommunicates bidirectionally with a port of controller 10. Theillustrative pacemaker of FIG. 1 may also include two ventricularsensing/pacing channels that include ring electrodes 23 a and 33 a, tipelectrodes 23 b and 33 b, sense amplifiers 21 and 31, pulse generators22 and 32, and ventricular channel interfaces 20 and 30. The electrodesare electrically connected to the device by means of a lead. The ringand tip electrode associated with each channel can be used for bipolarsensing or pacing or, as described below, different electrodes can beconnected to each channel through a switching circuit 70 to result indifferent unipolar sensing or pacing vectors. The sensing circuitry ofthe pacemaker may generate atrial and ventricular sense signals whenvoltages sensed by the electrodes exceed a specified threshold.

The illustrative pacemaker may also include an evoked response sensingchannel that includes an evoked response channel interface 50 and asense amplifier 51. The channel interfaces may include analog-to-digitalconverters for digitizing sensing signal inputs from the sensingamplifiers, registers that can be written to for adjusting the gain andthreshold values of the sensing amplifiers, and, in the case of theventricular and atrial channel interfaces, registers for controlling theoutput of pacing pulses and/or changing the pacing pulse amplitude, ifdesired.

The controller 10 of the pacemaker may control the overall operation ofthe device in accordance with programmed instructions stored in memory12. The controller 10 interprets sense signals from the sensing channelsand controls the delivery of pacing pulses in accordance with a pacingmode. The controller 10 may interface with a switching circuit 70through which the electrodes are connected to the sense amplifiers andpulse generators. The controller 10 may be configured to connect theamplifiers and/or pulse generators to selected tip or ring electrodes ofany of the sensing/pacing channels that connect through the switchingcircuit 70. Each sense amplifier may amplify the voltage differencebetween two inputs, and the inputs may be selected from any of the tipor ring electrodes or the pacemaker case or can 60, which may also beelectrically connected to the switching circuit. The controller 10 mayhave the capability of connecting a pulse generator such that a pacingvoltage pulse appears across any of the tip or ring electrodes or acrossan electrode and the can 60. A particular set of electrodes and one ormore pulse generators used to output pacing pulses may be referred toherein as a pacing configuration.

The switching circuit 70 may be implemented as an array of MOSFETtransistors controlled by outputs of the controller 10. FIG. 2 shows aschematic diagram of a portion of a switching circuit. In theillustrative switch circuit, a pair of MOSFET transistors Q1 and Q2along with an inverter INV form a double-pole switch that switches oneof the inputs to sense amplifier 51 between ring electrodes 23 a and 33a in accordance with a control signal CS from the controller 10. Theother input is shown as being connected to can 60, but in someinstances, it may also be switched to one of the electrodes by theswitching circuit. In a more complicated version of the same basicpattern, the switching circuit 70 may be able to switch the amplifierinputs or pulse generator outputs to any of the tip or ring electrodesof the sensing/pacing channels or to the can 60, as desired.

FIG. 3 is a block diagram of an illustrative signal processing module300. In some instances, the illustrative signal processing module 300may be configured to perform a comparison between an accelerometersignal and a stored template for cardiac activity. The illustrativesignal processing module 300 may be incorporated into the controller 10either as code executed by the microprocessor or as one or more discretehardware components, and may compare an accelerometer signal obtainedduring a pacing time window with a stored template for cardiac activity.The comparison may be performed in either the time domain or thefrequency domain, or both.

Pacing pulses produced by cardiac rhythm management devices canincidentally stimulate the phrenic nerve and cause contraction of thediaphragm of the patient. It is also possible for unipolar pacingconfigurations to produce a pacing vector that stimulates the pectoralmuscles overlying the internal electrodes of the can, resulting inso-called pocket twitch. Both skeletal muscle stimulation and nervestimulation can be annoying or painful to a patient. Abrupt contractionsof either the pectoral muscles or the diaphragm can impart anacceleration to the implanted housing of the pacemaker, and typicallyresults in a sensor signal that can be correlated to the unwantedstimulation.

To detect whether pacing pulses are producing such unwanted stimulation,the controller 10 may be configured to use the accelerometer 330 (orother sensor) to sense any accelerations experienced by the devicehousing (e.g. can) that coincide with the output of a pacing pulse.Contraction of the heart and the resulting heart sounds can impart anacceleration to the device housing (e.g. can) that coincides with apacing pulse. In order to distinguish desired stimulation (e.g. heartcapture) from unwanted stimulation (e.g. skeletal muscle contraction),signal processing techniques can be applied to the sensor signal.

In some instances, signal processing may make use of a wavelettransformation of an exertion level sensor signal such as anaccelerometer signal. The accelerometer signal may be converted into aset of wavelets, the set of wavelets including continuous wavelets,wavelets at a fine scale, and/or wavelets of a coarse scale. Waveletanalysis may be viewed as presenting the signal in a plot of thefrequency components of the signal versus time with a representation ofthe signal intensity by frequency in that domain. See FIGS. 4A-4D inwhich FIGS. 4A and 4C illustrate time domain signals from an exertionrelated signal (e.g. accelerometer) which includes no phrenic nervestimulation and an exertion related signal which does include phrenicnerve stimulation (PS), respectively. FIGS. 4B and 4D show anillustrative wavelet analyses (using Morlet wavelet processing)corresponding to the exertion related signals of FIGS. 4A and 4C,respectively.

Wavelet analysis may, for example, allow the signal to be characterizedas, for example, including large amplitude shallow deflections, largeamplitude steep deflections, small amplitude shallow deflections, orsmall amplitude steep deflections, and to determine whether thedeflections occur at a consistent time and frequency relative to thepacing signal, thereby being suitable for distinguishing phrenic nervestimulation related signals from other exertion related signals. In someinstances, the wavelet analysis may be derived using Morlet wavelets. Inyet other embodiments, the wavelet analysis may be derived usingcontinuous wavelets, and/or any other suitable wavelet signal processingtechnique.

Within a plot of the frequency components of the signal versus time witha representation of the signal intensity by frequency in that domainresulting from wavelet analysis such as that of FIGS. 4A and 4C, thefrequency and time components of a signal may be determined by viewingthe plot as a contour map of the signal intensity. In some cases, acontour that surrounds the region of maximum signal intensity may beselected and a centroid or center of mass of that contour may becomputed. One familiar with the wavelet plots in question will readilydetermine a signal intensity threshold appropriately elevated above thebackground signal intensity to serve to select an intensity levelcontour for the computation of the centroid. The frequency and timecorresponding to the centroid may then be taken to represent thedominant frequency and the corresponding time of the event. This is oneillustrative method of identifying a dominate frequency and thecorresponding time of an event.

An illustrative detection and analysis of exertion related signals isillustrated somewhat schematically in the flow diagram of FIG. 5. In theillustrative method, phrenic nerve stimulation detection is initiated(500) to sample the exertion related signal (502) for the duration ofseveral cardiac cycles of left ventricular cardiac activity (50-350 ms)which is stored and analyzed (504) to extract a dominant frequency. Thedominant frequency is then checked (506) to determine if the dominantfrequency falls within the phrenic nerve stimulation frequency band. Ifthe dominant frequency does not fall within the phrenic nervestimulation frequency band, phrenic nerve stimulation is determined tobe not present (512). If the dominant frequency does fall within thephrenic nerve stimulation frequency band, then the dominant frequencymay be further checked (508) to determine if the dominant frequencyoccurs within an appropriate time window relative to left ventricularstimulation pacing pulses. If this condition is also met, then phrenicnerve stimulation is determined to be present (510), and if not, phrenicnerve stimulation is determined not to be present (512). In someinstances, the dominant frequency component is determined as a mean, orother central tendency measure, of two or more dominant frequencycomponents identified for two or more pacing pulses.

Another illustrative detection and analysis scheme, which addsconfirmation of the detection of phrenic nerve stimulation, isillustrated schematically in the flow chart of FIG. 6, in which phrenicnerve stimulation detection is initiated (600), sampled (602), andanalyzed (604) to extract a dominant frequency. The dominant frequencymay be checked (606) to determine if the dominant frequency falls withina phrenic nerve stimulation frequency band as in the method of FIG. 5.Should the dominant frequency not fall within the phrenic nervestimulation frequency band, the analysis may continue by modifying (614)the atrio-ventricular timing to change the timing of heart sounds andrepeating the dominant frequency analysis. As before, when the dominantfrequency does fall within the phrenic nerve stimulation frequency band,the dominant frequency may be further checked (608) to determine if thedominant frequency occurs within an appropriate time window relative toleft ventricular stimulation pacing pulses. If this fails to be true,the analysis may continue by modifying (614) the atrio-ventriculartiming to change the timing of heart sounds, and the dominant frequencyanalysis may be repeated.

If the dominant frequency does fall within the phrenic nerve stimulationfrequency band and the dominant frequency occurs within an appropriatetime window relative to left ventricular stimulation pacing pulses, thesignal may be further checked (616) to see if the signal meets otherpredetermined signal quality criteria such as, for example, themagnitude of the dominant frequency peak being greater than themagnitude of other peaks in the data by a specified tolerance and/or apeak sharpness requirement is met whereupon the phrenic nervestimulation is deemed to be present (610). Should the signal fail tomeet the predetermined quality criteria, the atrio-ventricular timingmay again be changed (614), and the dominant frequency analysis cyclemay be repeated.

In some instances, the processing circuit may determine that the phrenicnerve of the patient has been stimulated if a dominant frequency from awavelet analysis is seen to occur at a substantially consistent timeafter each of two or more pacing pulses and at substantially consistentfrequencies (e.g. frequencies consistent with phrenic nervestimulation).

For the purpose of determining a predetermined phrenic nerve stimulationfrequency band and a predetermined appropriate time window relative toleft ventricular stimulation pacing pulses, information related to anumber phrenic nerve stimulation tests may be collected from the patientprior to programming, or from a number of other patients, and may thenbe analyzed by, for example, plotting the data as a frequency histogram(see FIG. 7) and/or as a time delay histogram (see FIG. 8). In bothinstances, the frequency and time associated with phrenic nervestimulation or the lack thereof may be determined from, for example, thecentroid of a region within the wavelet plot as discussed above. In therespective figures, accelerometer data from 20 patients was collectedand analyzed together. As can be seen in FIG. 7, the majority of phrenicnerve stimulations occurred in a frequency band between a lower bound(710) at about 7 Hz and an upper bound (720) at about 18 Hz. Similarly,in FIG. 8 it will be seen that the majority of phrenic nervestimulations occurred within a time window between a lower bound (810)of about 90 ms and an upper bound (820) of about 110 ms following a leftventricle pacing pulse.

FIG. 9 is a flow diagram illustrating an another illustrative method ofdetermining if phrenic nerve stimulation is present or absent in apatient. Following initiation (900) of phrenic nerve stimulationdetection, several cardiac cycles of data from a sensor such as anaccelerometer, minute ventilation sensor, electrical signal sensor,pressure sensor, an acoustic sensor, and the like may be sampled (902)and subjected to spectral analysis (904) by a processing circuit incommunication with a memory and the sensor. The output of the spectralanalysis may then be compared (906) to a stored template of detectedphrenic nerve stimulation. The stored template of a phrenic nervestimulation event may be a patient specific template or a populationbased template. In some cases, either template may subsequently bemodified and/or updated by the acquisition and incorporation ofsubsequent phrenic nerve stimulation events.

In this illustrative method, if the spectral analysis output matches thestored template of detected phrenic nerve stimulation, phrenic nervestimulation is deemed to be present (910). If the spectral analysisoutput does not match the stored template of detected phrenic nervestimulation, spectral analysis output may be compared (908) to a storedtemplate of cardiac activity in which phrenic nerve stimulation isabsent. If the spectral analysis output matches the stored template ofcardiac activity in which phrenic nerve stimulation is absent, phrenicnerve stimulation is deemed not to have occurred (912). If the spectralanalysis output does not match the stored template of cardiac activityin which phrenic nerve stimulation is present and does not match thestored template of cardiac activity in which phrenic nerve stimulationis absent, the sampling (902) of several cardiac cycles of sensor datais repeated and the analysis may be repeated.

In this example, the illustrative signal processing module 300 of FIG. 3may be incorporated into the controller 10, which may be considered aprocessing circuit, either as code executed by a microprocessor or asone or more discrete hardware components, and may be configured tocompare, for example, an accelerometer signal obtained during the pacingtime window with one or both of stored templates of cardiac activity inwhich phrenic nerve stimulation is present and of cardiac activity inwhich phrenic nerve stimulation is absent. The comparison may beperformed in the frequency domain. In some instances, the illustrativesignal processing module 300 may be a matched finite impulse responsefilter that performs a cross-correlation between the accelerometersignal and a previously recorded and stored recorded template. Thetemplates may be represented in that case by the filter coefficients ofthe matched filter (i.e., the impulse response of the filter correspondsto a time-reversed version of the template of cardiac activity). In someinstances, in addition to determining if the comparison of the spectralanalysis output to a phrenic nerve stimulation template to determine ifphrenic nerve stimulation has occurred, the spectral analysis output maybe compared to a non-phrenic nerve stimulation template to determine ifphrenic nerve stimulation has not occurred.

In some instances, signal processing may make use of an analysis of theaccelerometer or other exertion level sensor signal by examination of apower spectrum of the signals. For example, an illustrative method mayinclude: receiving a sensor signal for a time period after one or morepacing pulses, wherein the sensor signal is provided by a sensor thatcan sense a stimulation of the phrenic nerve of the patient; derive apower spectrum based on the received sensor signal during the timeperiod after the one or more pacing pulses; and determine if the phrenicnerve of the patient has been stimulated based, at least in part, on thederived power spectrum.

The power spectrum may be considered to be a plot of power divided byfrequency (dB/Hz) versus frequency (Hz) as illustrated in FIG. 10. Arepresentative power spectrum of an accelerometer output or otherexertion level sensor obtained when no phrenic nerve stimulation ispresent exhibits lower power at low frequencies as shown by curve 701.This curve 701 represents the power spectrum of an illustrativeacceleration sensor signal during a time window following a pacingpulse. In some cases, the power spectrum may be an aggregate powerspectrum corresponding to time periods following two or more pacingpulses. As can be seen, when phrenic nerve stimulation is present, thepower spectrum of the sensor signal may exhibit greater power at thoselow frequencies as shown by curve 703, both when the phrenic nervestimulation occurs relatively soon after the pacing pulse as well aswhen the phrenic nerve stimulation occurs relatively late (705) afterthe pacing pulse. When no phrenic nerve stimulation is present, thepower spectrum of the sensor signal may exhibit substantially lowerpower at those same low frequencies, as shown by curve 701. In somecases, the derived power spectrum may be compared to one or more powerspectrum templates, such as a power spectrum template that correspondsto phrenic nerve stimulation and/or a power spectrum template thatcorresponds to no phrenic nerve stimulation.

While these examples are described with respect to phrenic nervestimulation, it is contemplated that the same approach may be used todetect other unwanted stimulation events. In any event, once it isdetermined that unwanted stimulation is occurring with pacing pulses,the controller 10 may make adjustments in the operation of the device.In some cases, capture verification tests may be performed as the pacingpulse energy is reduced until a pacing pulse energy is found thatachieves both capture and produces no (or reduced) unwanted stimulation.In some instances, the pacing configuration can be varied. For example,different pacing vectors can be used by switching the output of a pulsegenerator to different electrodes with the switching circuit 70.Switching from a unipolar to a bipolar pacing configuration, forexample, may help reduce pacing pulses from causing pectoral musclecontractions or other unwanted stimulation. In some instances, thetiming of the pacing pulses may be changed. For example, the AV, VV orother delays may be changed to help alleviate or minimize the unwantedstimulation.

Other pacing configurations with different pacing vectors and/ordifferent time delays may be less likely to stimulate, for example, thephrenic nerve. In the case of multi-site pacing, different pacingconfigurations using fewer or different pacing sites may also be tried.The configuration of the pacemaker may be varied automatically by thepacemaker during an initial or subsequent programming phase; may bevaried manually by an operator during an initial or subsequentprogramming phase; and/or may be adaptively varied by the pacemaker inresponse to sensed phrenic nerve stimulation.

In the foregoing Description, various features have been groupedtogether in a limited number of examples for the purpose of streamliningthe disclosure. This method of disclosure is not to be interpreted asreflecting an intention that the examples require more features than areexpressly recited in each appended claim. Similarly, the failure of anysingle example to expressly recite a given subset of the features founddistributed among the descriptions of other examples is not to beinterpreted as reflecting an intention that the feature subset not beconsidered disclosed. It is contemplated that features, structures, orcharacteristics disclosed in one example can be used in other examples,whether or not explicitly described unless clearly stated to thecontrary.

Various modifications and alterations will become apparent to thoseskilled in the art without departing from the scope and principles ofthis disclosure, and it should be understood that this disclosure is notto be unduly limited to the particular examples set forth hereinabove.

What is claimed is:
 1. A system for cardiac rhythm managementcomprising: a pulse generator for generating pacing pulses forstimulating a heart of a patient; a memory; a sensor configured to sensea response to a stimulation of a phrenic nerve of the patient and toproduce a corresponding sensor signal; a processing circuit incommunication with the memory and the sensor, the processing circuitconfigured to: receive the sensor signal for a time after one or morepacing pulses; derive a time-frequency representation of the sensorsignal based on the received sensor signal using wavelets; identify adominant frequency component in the time-frequency representation ofsensor signal; determine if the dominant frequency component fallswithin a predetermined frequency range; identify a time of occurrence ofthe dominant frequency component relative to a corresponding pacingpulse; determine if the time of occurrence of the dominant frequencycomponent occurs within a predetermined time window; determine if thephrenic nerve of the patient has been stimulated based, at least inpart, on the time-frequency representation of the sensor signal suchthat the dominant frequency component falls within the predeterminedfrequency range and the dominant frequency component occurs within thepredetermined time window; store a phrenic nerve stimulation eventidentifier in the memory if the processing circuit determines that thephrenic nerve of the patient has been stimulated.
 2. The system of claim1, wherein the sensor includes one or more of an accelerometer, a minuteventilation sensor, an electrical signal sensor, a pressure sensor, andan acoustic sensor that is/are configured to sense a measure indicativeof stimulation of the phrenic nerve of the patient.
 3. The system ofclaim 1, wherein the sensor includes an accelerometer that is configuredto sense an acceleration indicative of a response to a stimulation ofthe phrenic nerve of the patient.
 4. The system of claim 1, wherein thedominant frequency component is a mean of two or more dominant frequencycomponents resulting from each of two or more pacing pulses.
 5. Thesystem of claim 1, wherein the dominant frequency component isdetermined by a centroid of a feature in a time-frequency representationof the sensor signal based on the received sensor signal using wavelets.6. The system of claim 1, wherein the time of occurrence of the dominantfrequency component relative to the predetermined time window isdetermined by a centroid of a feature in a time-frequency representationof the sensor signal based on the received sensor signal using wavelets.7. The system of claim 1, wherein the processing circuit furtherdetermines if the dominant frequency component meets a predeterminedquality threshold, and wherein the phrenic nerve of the patient isdetermined to have been stimulated when the dominant frequency componentmeets a predetermined quality threshold, the dominant frequencycomponent falls within the predetermined frequency range and thedominant frequency component occurs within the predetermined timewindow.
 8. The system of claim 1, wherein the pulse generator providesthe pacing pulse to the heart of the patient after an atrio-ventriculardelay, and wherein the pulse generator changes the atrio-ventriculardelay, and the processing circuit repeats the receiving throughdetermining steps to determine if the phrenic nerve of the patient hasbeen stimulated.
 9. The system of claim 1, wherein the time-frequencyrepresentation of the sensor signal is derived using Morlet waveletsand/or a continuous wavelet transform.
 10. The system of claim 1,wherein the processing circuit further is configured to generate pacingpulses for stimulating the heart of a patient that are anticipated toboth capture the heart and to minimize phrenic nerve stimulation by thegenerated pacing pulses; and determine if capture of the heart has beenachieved.
 11. A method for determining if a phrenic nerve of a patientis stimulated by one or more pacing pulses of a cardiac pacemaker,comprising: receiving a sensor signal for a time after one or morepacing pulses, wherein the sensor signal is provided by a sensor thatcan sense a stimulation of the phrenic nerve of the patient; determininga time-frequency representation of the sensor signal based on thereceived sensor signal; identifying a dominant frequency component inthe time-frequency representation of sensor signal; determining if thedominant frequency component falls within a predetermined frequencyrange; identifying a time of occurrence of the dominant frequencycomponent relative to a corresponding pacing pulse; determining if thetime of occurrence of the dominant frequency component occurs within apredetermined time window; and determining if the phrenic nerve of thepatient has been stimulated based, at least in part, on thetime-frequency representation of the sensor signal such that thedominant frequency component falls within the predetermined frequencyrange and the dominant frequency component occurs within thepredetermined time window.